This invention relates generally to the field of methods for guiding the treatment of cancer patients with chemotherapy agents. More particularly, this invention relates to a method of predicting, in advance of initiating treatment, whether a patient is a member of a class of patients that are unlikely to benefit from administration of platinum-based chemotherapy agents, such as cisplatin, carboplatin, and analogs thereof. The methods of this disclosure use mass spectral data obtained from a blood-based sample of the patient, a computer configured as a classifier operating on the mass spectral data, and a training set comprising class-labeled spectra from other cancer patients.
The assignee of the present invention, Biodesix, Inc., has developed a test known as VeriStrat. One of the uses of VeriStrat is that it predicts whether Non-Small Cell Lung Cancer (NSCLC) patients are likely or not likely to benefit from treatment with drugs targeting the Epidermal Growth Factor Receptor (EGFR) pathway, e.g. EGFR inhibitors such as erlotinib. The test is described in U.S. Pat. No. 7,736,905, the content of which is incorporated by reference herein. Additional applications of the test are also described in U.S. Pat. Nos. 7,858,390; 7,858,389 and 7,867,775, the contents of which are incorporated by reference herein.
In brief, the VeriStrat test is based on serum and/or plasma samples of cancer patients. Through a combination of MALDI-TOF mass spectrometry and data analysis algorithms implemented in a computer, the commercial version of the test compares a set of eight integrated peak intensities at predefined m/z ranges in the mass spectrum of the patient sample (after pre-processing steps are performed) with those from a training cohort, and generates a class label for the patient sample: either VeriStrat Good, VeriStrat Poor, or VeriStrat “indeterminate.” In multiple clinical validation studies it has been shown that patients, whose pre-treatment serum/plasma is classified as VeriStrat Good, have significantly better outcome when treated with epidermal growth factor receptor inhibitor drugs than those patients whose sample is classified as VeriStrat Poor. In a few cases (less than 2%) no determination can be made, resulting in a VeriStrat indeterminate label.
The applicants have further discovered that the VeriStrat test is also predictive for whether head and neck squamous cell carcinoma and colorectal cancer patients are likely to have better or worse outcomes from treatment with certain anti-cancer drugs, as described in U.S. Pat. Nos. 8,024,282; 7,906,342; 7,879,620; 7,867,775; 7,858,390; 7,858,389 and 7,736,905.
In pending U.S. patent application Ser. No. 13/356,730 filed Jan. 24, 2012, we have described how the VeriStrat test also predicts that breast cancer patients having the VeriStrat Poor signature are unlikely to obtain good clinical outcomes from endocrine therapy alone, including for example an aromatase inhibitor such as letrozole. In that document, we have also described how hormone receptor positive breast cancer patients, regardless of their HER2 status, which have the VeriStrat Poor signature are likely to benefit from administration of a combination treatment comprising administration of a targeted anti-cancer drug in addition to an endocrine therapy drug.
Platinum-based chemotherapy drugs, including cisplatin (cis-PtCl2(NH3)2) and analogs thereof, are used to treat various kinds of cancers, including sarcomas, lymphomas, and carcinomas. The drug reacts in vivo, binding to and causing crosslinking of DNA, which interferes with cell division by mitosis, ultimately triggering apoptosis (programmed cell death). Cisplatin combination therapy is a cornerstone of treatment of many cancers. However, while initial platinum responsiveness is high, some patients do not respond to treatment, and the majority of cancer patients will eventually relapse with cisplatin resistant disease. There is a need in the art to be able to predict in advance of treatment whether a patient will not obtain benefit from cisplatin (alone or in combination treatment) as if this determination can be made at an early stage in treatment the patient can be guided towards other non-platinum therapies that are more likely to provide clinical benefit. This invention meets that need.